Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes

L Carraresi; S A Tripodi; L C Mulder; S Bertini; S Nuti; K Schuerfeld; M Cintorino; G Bensi; M Rossini; M Mora

doi:10.1038/sj.onc.1205007

Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes

Oncogene. 2001 Dec 6;20(56):8148-53. doi: 10.1038/sj.onc.1205007.

Authors

L Carraresi¹, S A Tripodi, L C Mulder, S Bertini, S Nuti, K Schuerfeld, M Cintorino, G Bensi, M Rossini, M Mora

Affiliation

¹ Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro, 53100 Siena, Italy.

PMID: 11781829
DOI: 10.1038/sj.onc.1205007

Abstract

Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age.

MeSH terms

Animals
Carcinoma / complications
Carcinoma / pathology
Carcinoma / virology*
Keratin-15
Keratin-5
Keratins / genetics*
Liver Neoplasms / complications
Liver Neoplasms / pathology
Liver Neoplasms / secondary
Lung Neoplasms / complications
Lung Neoplasms / pathology
Lung Neoplasms / virology*
Mice
Mice, Transgenic
Oncogene Proteins, Viral / genetics
Oncogene Proteins, Viral / pharmacology*
Organ Size
Papillomavirus E7 Proteins
Papillomavirus Infections / complications
Papillomavirus Infections / pathology*
Promoter Regions, Genetic
Recombinant Fusion Proteins / pharmacology
Repressor Proteins*
Thymus Gland / pathology
Thymus Hyperplasia / complications
Thymus Hyperplasia / pathology
Thymus Hyperplasia / virology*
Tumor Virus Infections / complications
Tumor Virus Infections / pathology*

Substances

E6 protein, Human papillomavirus type 16
KRT5 protein, human
Keratin-15
Keratin-5
Krt15 protein, mouse
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Recombinant Fusion Proteins
Repressor Proteins
oncogene protein E7, Human papillomavirus type 16
Keratins